Int. J. Mol. Sci. 2013, 14(2), 3802-3816; doi:10.3390/ijms14023802
Article

Downregulation of miR-17~92 Expression Increase Paclitaxel Sensitivity in Human Ovarian Carcinoma SKOV3-TR30 Cells via BIM Instead of PTEN

1email, 1,2,†email, 1,†email, 1,* email and 1email
1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China 2 Shenyang Maternity and infant Hospital, 90 Qingnian Road, Shenhe District, Shenyang 110014, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 24 December 2012; in revised form: 23 January 2013 / Accepted: 4 February 2013 / Published: 8 February 2013
(This article belongs to the Special Issue Regulation by non-coding RNAs)
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Abstract: To better understand the molecular mechanisms of paclitaxel resistance in ovarian carcinoma, we evaluated the expression of miRNAs using miRNA microarray between human ovarian carcinoma SKOV3 cells and paclitaxel resistant SKOV3-TR30 cells. Results showed that 69 miRNAs were upregulated while 102 miRNAs were downregulated in SKOV3-TR30 cells. Using real-time PCR, we further clarified that miR-17~92 was overexpressed in SKOV3-TR30 cells compared with that in SKOV3 cells. We then established stable virally transduced SKOV3-TR30-m-PTIP-Sponge all SKOV3-TR30 cells and its vector-only control SKOV3-TR30-m-PTIP-GFP cells. Real time-PCR revealed that SKOV3-TR30-m-PTIP-Sponge all cells expressed approximately 6.18-fold lower levels of miR-17~92 compared with the control group. Decreased expression of miR-17~92 resulted in cell cycle arrest in the G2/M phase and growth inhibition. After the transduction, the BIM protein level was increased in SKOV3-TR30 cells and luciferase reporter assays revealed that miR-17~92 binds directly to the 3'-UTR of BIM. Results of luciferase reporter assays accompanied with Western Blot showed that although miR-17~92 binds directly to the 3'-UTR of PTEN, the PTEN protein expression level was upregulated slightly while the result is of no statistical significance. Our results showed that miR-17~92 could be a causal factor of the downregulation of BIM in SKOV3-TR30 cells and thus induce the paclitaxel resistance in SKOV3-TR30 cells.
Keywords: miR-17~92 cluster; transduction; ovarian carcinoma; paclitaxel resistance; PTEN; BIM

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MDPI and ACS Style

Shuang, T.; Shi, C.; Chang, S.; Wang, M.; Bai, C.H. Downregulation of miR-17~92 Expression Increase Paclitaxel Sensitivity in Human Ovarian Carcinoma SKOV3-TR30 Cells via BIM Instead of PTEN. Int. J. Mol. Sci. 2013, 14, 3802-3816.

AMA Style

Shuang T, Shi C, Chang S, Wang M, Bai CH. Downregulation of miR-17~92 Expression Increase Paclitaxel Sensitivity in Human Ovarian Carcinoma SKOV3-TR30 Cells via BIM Instead of PTEN. International Journal of Molecular Sciences. 2013; 14(2):3802-3816.

Chicago/Turabian Style

Shuang, Ting; Shi, Chunxue; Chang, Shuang; Wang, Min; Bai, Cui H. 2013. "Downregulation of miR-17~92 Expression Increase Paclitaxel Sensitivity in Human Ovarian Carcinoma SKOV3-TR30 Cells via BIM Instead of PTEN." Int. J. Mol. Sci. 14, no. 2: 3802-3816.

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